Within the last year, cytochrome c release from the mitochondria has been identified as a very early event during apoptosis, or programmed cell death. Furthermore, a loss of mitochondrial membrane potential is observed during the mitochondrial permeability transition, which results from oxidative stress injuries. This has led us to inquire whether multiphoton imaging of mitochondrial NADH may provide a technique to observe mitochondrial dysfunction without the use of exogenous mitochondrial probes. Our recent efforts have been directed at establishing protocols to induce apoptosis and/or mPT in rodent and/or human cancer cell lines. Future experiments will seek to correlate changes in mitochondrial autofluorescence with mitochondrial morphology and membrane potential as observed with fluorescent probes.